The Role of Human Dendritic Cells in Cutaneous Allergen Recognition and Immune Activation

Rationale: Dendritic cells (DCs) initiate the immune response against a wide range of pathogens.  There is evidence in the mouse that Th1 versus Th2 differentiation is defined by the DC subset that activates naïve T cells, however, the analogous DC subsets in the human have yet to be determined.  We sought to identify the DC subset responsible for Th2 skewing in human skin. 

Methods: Using an ex vivo human skin explant model, we analyzed the DCs that responded to and migrated out of skin specifically in response to novel allergen exposure (papain) versus exposure to the non-allergenic protein ovalbumin (OVA). DCs were phenotyped by flow cytometry.

Results: We identified three populations of CD45⁺CD11c⁺HLA-DR⁺ DCs which preferentially migrated out of the skin in response to papain immunization: CD14^-/CD16^- DCs (5-fold increase compared to OVA), CD14⁺ DCs (2-fold increase compared to OVA), and CD16⁺CD1c⁺ (3-fold increase compared to OVA).  Expression of costimulatory and activation markers significantly varied between these groups, with the CD16⁺CD1c⁺ population expressing high levels of CD86 and PD-L2.

Conclusions: We have identified three subpopulations of human dermal DCs that preferentially migrate out of the skin in response to primary exposure to an allergen.  The CD16⁺CD1c⁺ population expressed high levels of PD-L2, which has also been shown to be elevated in a Th2 skewing dermal DC population in the mouse.  Further characterization of these cells will improve our understanding of the function and role of these DC subsets, and may provide an additional therapeutic target for the treatment of allergic diseases.